NEONATAL JAUNDICE urobilinogen- excreted through feces

Dr.Joselito F. Villaruz
June 26, 2013
By Group TwoBig

ILO:
 Describe bilirubin metabolism
 Discuss the causes of unconjugated hyperbilirubinemia
 Discuss the causes of conjugated hyperbilirubinemia
 Discuss physiologic and pathologic jaundice
 Plan diagnostic approach in a neonate presenting with
jaundice
 Discuss the complications of severe unconjugated
hyperbilirubinemia
 Discuss the various modalities of treatment and the
principles involved

NEONATAL JAUNDICE I. CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA

 A common phenomenon A. Increased bilirubin load to the liver for conjugation
 seen in 60% of term infants and 80% of preterms during 0. Hemolyticanemias
the first week of life A. Polycythemia
 Results from accumulation of bilirubin B. Bruising/internal hemorrhage
C. Shortened RBC life (immaturity/transfusion)
TYPES: D. Increased entero-hepatic circulation
1. Indirect acting (B1) E. Infections
0. Unconjugated B. Ineffective/reduced activity of glucuronyltransferase
1. Non-polar, hydrophobic and other related enzymes
2. Lipid-soluble • Genetic deficiency
3. Potentially neurotoxic • Hypoxia
2. Direct - reacting (B2) • Infections
4. Conjugated • Hypothyroidism
5. Water-soluble C. Competitive inhibition for tranferase enzyme
6. Polar, hydrophilic • Drugs/other substances
7. May indicate potentially serious hepatic disorders, D. Absence/decreased amount of enzymes
systemic diseases • Genetic defects
 Naming of direct and indirect Bilirubin- based on Van den • Prematurity
Bergh Reaction FACTORS FAVORING UNCONJUGATED BILIRUBIN NEUROTOXITY
 Direct-measured directly
 Indirect-obtained by subtracting direct from total Bilirubin
1. Hypoproteinemia
Decrease in albumin-> unconjugated bilirubin unbound to
albumin crosses BBB
ETIOLOGY:
Neonatal period is transition phase from fetal stage to adult 2. Displacement of biliruibin from albumin-binding sites
stage of bilirubin excretion (drugs: sulfas, Moxalactam, VitK3)
3. Acidosis
 Fetal stage – elimination through placenta 4. Increased fatty acid concentration due to hypoglycemia,
 Adult stage – elimination through conjugation in the starvation, hypothermia
hetapocytes into the biliary and GIT 5. Increased permeability of the blood brain barrier
BILIRUBIN METABOLISM
6. Neural susceptibillity to injury (asphyxia, prematurity,
hyperosmolarity, infections)
II. CAUSES OF CONJUGATED HYPERBILIRUBINEMIA
A. Neonatal hepatitis
Cholestasis
 delayed excretion to the biliary tree
B. Perinatal congenital infection ( TORCH)
C. Mechanical obstruction
 Biliary atresiaDubin-Johnson Syndrome
 Rotor's Syndrome
 Choledochal cyst

RISK FACTORSfor development of SEVERE HYPERBILIRUBINEMIA in

infants≥35weeks of gestation (in approx. order of importance)
90%

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MAJOR RISK FACTORS Indirect bilirubin hue is bright
1. Predischarge TSB(total serum bilirubin)/TcB (Transcutaneous yellow or orange
measurement) level in the high risk zone
2. Jaundice observed in the 1st 24 hrs –almost exclusively due to Direct bilirubin hue is greenish or
hemolyticd.o)
muddy yellow
3. Blood grp incompatibility with positive direct antiglobulin test,
other known hemolytic disease (glucose-6-phosphate Other signs and symptoms:Early
dehydrogenase deficiency), elevated end-title CO signs of neurotoxicity
concentration  Lethargy
4. Gestational age 35-36 week  Poor feeding
5. Previous sibling received phototherapy  Encephalopathy
6. Cephalhematoma (NO ASPIRATION!) or significant bruising LABORATORY EVALUATION of jaundiced infant ≥35 weeks of
7. Exclusive breast-feeding, particularly if nursing is not going well gestation
and weight loss is excessive
INDICATIONS ASSESSMENTS
8. East Asian race- Asian greater risk than Caucasians
Jaundice in first 24 hr Measure TcB and/or TSB
MINOR RISK FACTORS Jaundice appears Measure TcB and/or TSB
Predischarge TSB or TcB level in the high intermediate-risk zone excessive for infant's age
Gestational age 37-38 week
Infant receiving Blood type and Coombs test, if not
Jaundice observed before discharge
phototherapy or TSB rising obtained with cord blood
Previous sibling with jaundice
rapidly (i.e., crossing Complete blood count-(Why?RBC, for
Macrosomic infant of a diabetic mother
percentiles and hemolysis& WBC for sepsis) and smear
Maternal age ≥25 yr
unexplained by history (Why?RBChemolysis: spherocyctes,
Male gender
and physical examination microspherocytes, irregularly –shaped cells)
Measure direct or conjugated bilirubin
DECREASED RISK (these factors are associated with decreased risk of
significant jaundice, listed in order of decreasing importance) It is an option to perform reticulocyte
TSB or TcB level in the low-risk zone count, G6PD, and ETCOc, if available
Gestational age ≥41 wk Repeat TSB in 4-24 hr depending on infant's
Exclusive bottle-feeding age and TSB level
Black race TSB concentration Perform reticulocyte count, G6PD, albumin,
Discharge from hospital after 72 hr approaching exchange ETCOc, if available
levels or not responding to
CLINICAL MANIFESTATIONS phototherapy
• May be present at any time during the neonatal period Elevated direct (or Do urinalysis and urine culture
depending on the etiology conjugated) bilirubin level
• Starts from the face then proceeds caudally Evaluate for sepsis if indicated by history
• Dermal pressure may reveal anatomic progression and physical examination
Jaundice present at or Total and direct (or conjugated) bilirubin
beyond age 3 wk, or sick level
infant If direct bilirubin elevated, evaluate for
FACE = 5 mg/dl causes of cholestasis
MID ABDOMEN = 15 mg/dl
Check results of newborn thyroid and
(if with s/sx, risk factors – may require
galactosemia screen, and evaluate infant
evaluation)
for signs or symptoms of hypothyroidism
SOLES = 20 mg/dl
DIFFERENTIAL DIAGNOSES
*Evaluate in Jaundice started at <24h of age
well-lighted area  Hemolytic disorder
Transcutaneous measurement of bilirubin (TcB)  Rhesus incompatibility
• may be used to screen infants  ABO incompatibility
• Non-invasive  G6PD defiency
• Not accurate  Spherocytosis
 Serum levels necessary if TcB is elevated for age-specific  Pyruvate kinase deficiency
measurements, progressing jaundice, risk for hemolysis/sepsis  Congenital infection
SKIN COLOR  Cephalhematoma
Jaundice started at 2nd to 3rd day
 Physiologic
 Early onset breastfeeding jaundice
 Crigler-Najjar Syndrome (Familial non-hemolytic icterus)
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Jaundice started after the 3rd day-7th day C. Pattern
 Bacterial sepsis *At times may be physiologic but factors exist placing the infant
 UTI at special risk for neurotoxicity
 TORCH, enteroviruses
Jaundice started after the 1st week a. Hemolytic Disorder
 Breastmilk jaundice 1. Rhesus hemolytic disease
 Sepsis (Rh Incompatibility)
 Congenital atresia/paucity of biliary tracts -usually identified antenatally and monitored if necessary
 Hepatitis
 Galactosemia Rh(-) mom
 Hypothyroidism
 Cystic fibrosis
 Congenital hemolytic crisis due to enzyme deficiencies/
RBC defect

Rh (+)
Persistent Jaundice during the 1st month of life
 Cholestasis secondary to hyperalimentation baby
*This usually occurs with severe intrauterine hemolysis, anemia
 Hepatitis
and congestive high output failure.
 Cytomegalic Inclusion Disease, syphilis, toxoplasmosis
C. ABO incompatibility
 CriglerNajjar
• More common than Rhesus incompatibility
 Biliary Atresia
• Most ABO antibodies are IgM
 Inspissated bile syndrome
• Some group of O women have IgG anti-A
hemolysin in blood which can crossthe placenta
CRIGLER–NAJJAR SYNDROME or CNS and hemolyse the red cell of a group A infant
 is a rare disorder affecting the metabolism of bilirubin, a • Group B infant will be affected by anti-B
chemical formed from the breakdown of red blood cells. hemolysin
The disorder results in an inherited form of non- • Diagnosed by Coomb’s test
hemolytic jaundice, which results in high levels of CLINICAL FEATURES OF HEMOLYTIC DISEASE
unconjugated bilirubin and often leads to brain damage Clinical Features Rh ABO
in infants. Frequency Unusual Common
Anemia Marked Minimal
A. PHYSIOLOGIC JAUNDICE Jaundice Marked Minimal to
Risk factors: moderate
 Maternal age Hydrops Common Rare
 Oriental race
Hepatosplenomegaly Marked Minimal
 Maternal DM
Kernicterus Common Rare
 Prematurity
LABORATORY FEATURES OF HEMOLYTIC DISEASE
 Drugs (Vitamin K3)
 Altitude/polycythemia Laboratory Features Rh ABO
 Male sex Blood type of Rh negative
O
 Losses (dehydration/caloric deprivation) Mother
 Delayed passage of meconium Blood type of Infant Rh positive A or B
 (+) family history of physiologic diagnosis Anemia Marked Minimal
DIAGNOSIS MADE BY EXCLUSION Direct Coomb’s test
 Indirect bilirubin levels in full term infants decline to adult Positive Negative
levels by 10-14 days
 If PERSISTENT, think of pathologic causes Indirect Coomb’s Usually positive
Investigation warranted if: Positive
test
1. Jaundice appears in the 1st 24-36 hrs of life Hyperbilirubinemia marked Variable
2. Levels rising >5mg/dl/24 hrs RBC morphology Nucleated RBC Spherocytes
3. Bilirubin >12mg/dl in a full term infant and >14 mg/dl in C. G6PD deficiency
preterms without risk factors • Mainly affect male infants
• an inherited disorder of the red blood cell
4. Jaundice persists after 10-14days
• the red blood cells are prone to haemolysis
5. Direct fraction of >2mg/dl at any time when exposed to oxidants or when certain foods
B. PATHOLOGIC JAUNDICE or herbs are ingested
 Considered if it varies significantly from physiologic D. Polycythemia
jaundice in terms of:  The liver may not have the capacity to
A. Timing of appearance metabolize the increased bilirubin load
B. Duration presented by the increased blood volume

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 5. Cephalhematoma CLINICAL FEATURES
 Subperiosteal bleed Phase 1 (1st 1-2 days): poor suck, stupor, hypotonia,
 Lasts for months in some cases seizures
ACUTE
FORM Phase 2 (middle of 1st wk): hypertonia of extensor
JAUNDICE ASSOCIATED WITH BREASTFEEDING muscles, opisthotonos, retrocollis, fever
A. Breastmilk jaundice
0. Seen in 2% of breastfed term infants Phase 3 (after the 1st wk): hypertonia
A. Occurs after the 7th day 1st year: hypotonia, active deep tendon reflexes,
B. Maximum bilirubin concentration 10-30 mg/dl at the CHRONIC
obligatory tonic neck reflexes, delayed motor skills
2nd-3rd week FORM After 1st yr: movement disorders (choreoathetosis,
C. May persist for weeks if breastfeeding is continued ballismus, tremor), upward gaze, sensorineural hearing
but at relatively lower levels loss
D. Rapid fall in bilirubin when breastfeeding is INCIDENCE & PROGNOSIS
discontinued • Develops in 30% of infants with untreated hemolytic
E. Phototherapy may be of benefit disease and bilirubin levels > 25-30 mg/dl
F. Kernicterus uncommon • Infants who progress to severe neurologic signs die
G. Attributed to glucorunidase in breastmilk • > 75% of patients die
(pregnanediol) • 80% of affected survivors have sequelae
B. Breastfeeding Jaundice • Chorio-athetoid cerebral palsy
0. Occurs within the 1st week of life • Sensori-neural hearing loss
A. Higher bilirubin levels than formula fed infants • Upward gaze palsy
B. Bilirubin may increase to >12 mg/dl in 13% of cases • Dental-enamel dysplasia
Attributed to: • Mental retardation
 Decreased milk intake with dehydration • Speech disturbance
 Reduced caloric intake PREVENTION
Management: • Universal screening for hyperbilirubinemia in the 1 st 24-48
 Frequent breastfeeding hours of life to detect infants at high risk for severe
 Rooming in with night feeding jaundice and bilirubin-induced neurologic dysfunction
 Lactation support • Vigilance and system-based approach
KERNICTERUS • Use of hour-specific bilirubin nomogram, PE and clinical
• Bilirubin encephalopathy risk factors
• Deposition of indirect bilirubin in the basal ganglia and Preventable Causes of Kernicterus (AAP)
brainstem nuclei  Early discharge (<48 hrs) with no early follow up
• Pathogenesis: multifactorial  Failure to check bilirubin in a jaundiced infant in the 1st 24
• Unbound unconjugated bilirubin levels hours of life
• Albumin binding  Failure to recognize the presence of risk factors
• Permeability of the BBB  Underestimating the severity of jaundice
• Neuronal susceptibility to injury  Lack of concern regarding presence of jaundice
• Precise toxic level is UNPREDICTABLE – usually levels >  Delay in getting serum levels/delay in initiating
20mg/dl phototherapy
• Duration of exposure to produce toxicity: UNKNOWN  Failure to respond to parental concern on jaundice and
• Pretermsare more susceptible other s/sx

Risk designation of term and near-term well newborns based on

their hour-specific serum bilirubin values. Bhutani VK, Johnson L,
Sivieri EM: Predictive ability of a predischarge hour-specific serum
bilirubin for subsequent significant hyperbilirubinemia in healthy
term and near-term newborns, Pediatrics 103:6–14, 1999.

MANAGEMENT OF HYPERBILIRUBINEMIA

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General Goal: prevent neurotoxicity due to B1 levels • Light energy emitted in the effective range of wavelengths
Modalities of treatment: • The distance between the lights and the infant
 Phototherapy • Surface area of the exposed skin
 Exchange transfusion • Rate of hemolysis and in vivo metabolism and excretion of
Guidelines for Phototherapy Treatment bilirubin
*dark skin does not reduce the efficacy of phototherapy

Guidelines for Exchange Transfusion

EXCHANGE TRANSFUSION
• Double volume exchange transfusion (DVET)
• Performed if intensive phototherapy has failed and the risk
of kernicterus exceeds the risks of the procedure
• Indicated when clinical signs suggestive of kernicterus are
apparent
Total volume to be infused and to be removed after is:
• TOTAL BLOOD VOLUME (constant, depend on age) x WEIGHT
(kg) x 2
e.g: 2kg neonate
PHOTOTHERAPY ( 70-90 ml/kg) x 2kg x 2 = 280-360ml
• Reduction of hyperbilirubinemia by exposure to high • OBJECTIVES:
intensity light in the visible spectrum • To reduce the serum bilirubin level and reduce
• Broad-spectrum white, blue and special narrow spectrum the risk of brain damage and kernicterus
(super) blue lights • To remove the infant’s sensitized red blood cells
• Mechanism:reversible photoisomerization of bilirubin and the circulating antibodies, reduce the degree
when light is absorbed by the skin of red cell destruction
• May reduce the need for repeated exchange transfusions
• Applied continuously and infant is turned frequently for
maximum exposure
• Serum bilirubin levels are monitored every 4-8 hours in
infants with hemolytic disease
• Bilirubin monitoring should continue 24 hours after
cessation of phototherapy as rebound jaundice may occur
• Skin color evaluation is UNRELIABLE
• From native unconjugated (cis-form) to an unconjugated
water-soluble isomer, LUMIRUBIN(trans-form)
Porphyria is contraindicated in phototherapy

Factors Affecting Response to Phototherapy

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#VIGINTIPHOBIA

 “A fear of the number 20”

 Term published from the journal Pediatrics, entitled, “Bilirubin
20 mg/dL = vigintiphobia” in 1983.
 The article reinforced the premise set forth previously in the
pediatric literature that hyperbilirubinemia among otherwise
healthy term infants without hemolysis posed a lower risk for COMPLICATIONS:
kernicterus than did hyperbilirubinemia secondary to hemolytic Catheter related
disease.  infection
 The commentary also suggested that exchange transfusion at a  hemorrhage
total serum bilirubin (TSB) level of 20 mg/dL(340 μmol/L) under  necrotizing enterocolitis
such circumstances might not be warranted.  air embolism
The commentary prompted a comprehensive detailed review and  portal and splenic vein
reanalysis of existing studies of nonhemolytic neonatal  thrombosis (late sequelae)
hyperbilirubinemia
Haemodynamic problems
 overload cardiac failure
 hypovolemic shock
ONE CATHETER PUSH PULL  arrhythmia (catheter tip near sinus node in right atrium)
 bradycardia with calcium bolus
Blood
Electrolyte imbalance
 hyperkalemia
 hypocalcemia OUTLINE
IN LINE Blood Fillter
 hyper- and hypo-glycemia
 metabolic acidosis, alkalosis (late breakdown of citrate)

QUIZ! One Way Valve

TRUE OR FALSE
1. Unconjugated bilirubin is water-soluble.
ALARIS 2. Immune mediated hemolysis presents as jaundice starting
Giving Set by the 2nd day of life.
3. 50 % of the bilirubin secreted into the small intestine are
Heating
acted upon Umbilical Vein and reverted back into the portal
by proteases
circulation. Catheter
Empty
4. Male neonates are moreBottle at risk than their female
counterparts.
TWO CATHETER PUSH-PULL
5. Transcutaneous bilirubin determination is the gold
standard used in diagnostic evaluation of neonatal
jaundice.
6. Lumirubin, a bilirubin isomer is unconjugated bilirubin.
7. A 3 kg newbornwho is to undergo double volume exchange
transfusion will need approximately 240-270 ml of fresh
whole blood.
8. The diagnosis of physiologic jaundice is based on the
serum bilirubin levels
9. ABO incompatilibity occurs with the mother is type O and
the baby is type A/B
10. ABO incompatibility is diagnosed by direct Coomb’s test.

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